Sanjay K. Banerjee

EFFECT OF GARLIC ON CARDIOVASCULAR DISORDERS: A REVIEW

Garlic and its preparations have been widely recognized as agents for prevention and treatment of cardiovascular and other metabolic diseases, atherosclerosis, hyperlipidemia, thrombosis, hypertension and diabetes. Effectiveness of garlic in cardiovascular diseases was more encouraging in experimental studies, which prompted several clinical trials. Though many clinical trials showed a positive effect of garlic on almost all cardiovascular conditions mentioned above, however a number of negative studies have recently cast doubt on the efficary of garlic specially its cholesterol lowering effect of garlic. It is a great challenge for scientists all over the world to make a proper use of garlic and enjoy its maximum beneficial effect as it is the cheapest way to prevent cardiovascular disease. This review has attempted to make a bridge the gap between experimental and clinical study and to discuss the possible mechanisms of such therapeutic actions of garlic.

Protection against acute adriamycin-induced cardiotoxicity by garlic: Role of endogenous antioxidants and inhibition of TNF-α expression

BackgroundOxidative stress is the major etiopathological factor in adriamycin-induced cardiotoxicity. Relatively low amounts of endogenous antioxidant makes the heart vulnerable to oxidative stress-induced damage. Chronic oral administration of garlic has been reported to enhance the endogenous antioxidants of heart. We hypothesized that garlic-induced enhanced cardiac antioxidants may offer protection against acute adriamycin-induced cardiotoxicity.ResultsRats were either administered freshly prepared garlic homogenate (250 and 500 mg/kg daily, orally, for 30 days) or probucol (cumulative dose, 120 mg/kg body weight divided in 12, i.p. over a period of 30 days) or double distilled water (vehicle), followed by a single dose of adriamycin (30 mg/kg i.p.). In the adriamycin group, increased oxidative stress was evidenced by a significant increase in myocardial TBARS (thiobarbituric acid reactive substances) and decrease in myocardial SOD (superoxide dismutase), catalase and GPx (glutathione peroxidase) activity. Histopathological studies showed focal as well as subendocardial myocytolysis with infiltration of macrophages, lymphocytes and edema. Immunocytochemistry showed marked expression of TNF-α (tumor necrosis factor-alpha) in the myocardium. Increase in myocardial TBARS and decrease in endogenous antioxidants by adriamycin was prevented significantly in the garlic treated rat hearts, which was comparable to the probucol-treated group. Histopathological evidence of protection was also evident in both garlic-treated and probucol-treated groups. Probucol, 250 mg/kg and 500 mg/kg of garlic reduced adriamycin induced TNF-α expression in the myocardium and was associated with reduced myocyte injury.ConclusionsIt is concluded that chronic garlic administration prevents acute adriamycin-induced cardiotoxicity and decreases myocardial TNF-α expression.

Activation of mammalian target of rapamycin controls the loss of TCRzeta in lupus T cells through HRES-1/Rab4-regulated lysosomal degradation.

Persistent mitochondrial hyperpolarization (MHP) and enhanced calcium fluxing underlie aberrant T cell activation and death pathway selection in systemic lupus erythematosus. Treatment with rapamycin, which effectively controls disease activity, normalizes CD3/CD28-induced calcium fluxing but fails to influence MHP, suggesting that altered calcium fluxing is downstream or independent of mitochondrial dysfunction. In this article, we show that activity of the mammalian target of rapamycin (mTOR), which is a sensor of the mitochondrial transmembrane potential, is increased in lupus T cells. Activation of mTOR was inducible by NO, a key trigger of MHP, which in turn enhanced the expression of HRES-1/Rab4, a small GTPase that regulates recycling of surface receptors through early endosomes. Expression of HRES-1/Rab4 was increased in CD4+ lupus T cells, and in accordance with its dominant impact on the endocytic recycling of CD4, it was inversely correlated with diminished CD4 expression. HRES-1/Rab4 overexpression was also inversely correlated with diminished TCRζ protein levels. Pull-down studies revealed a direct interaction of HRES-1/Rab4 with CD4 and TCRζ. Importantly, the deficiency of the TCRζ chain and of Lck and the compensatory up-regulation of FcεRIγ and Syk, which mediate enhanced calcium fluxing in lupus T cells, were reversed in patients treated with rapamcyin in vivo. Knockdown of HRES-1/Rab4 by small interfering RNA and inhibitors of lysosomal function augmented TCRζ protein levels in vitro. The results suggest that activation of mTOR causes the loss of TCRζ in lupus T cells through HRES-1/Rab4-dependent lysosomal degradation.

Dose-dependent induction of endogenous antioxidants in rat heart by chronic administration of garlic

The inhibitory property of garlic on free radical generation and lipid peroxidation has been reported in a number of in vitro studies. However, the in vivo effects of chronic garlic intake on the antioxidant milieu of heart has not been reported. Therefore, the present study was designed to investigate the effect of chronic garlic homogenate administration on myocardial endogenous antioxidants and lipid peroxidation at five different dosage levels (125, 250, 500, 1000 and 2000 mg/kg; B, C, D, E, F groups respectively). Garlic homogenate was administered orally to Wistar albino rats (150-200 gms) of either sex 6 days/week for 30 days. Myocardial TBARS (Thiobarbituric acid reactive substances) and antioxidants such as SOD (Superoxide Dismutase), catalase, GPx (glutathione peroxidase) and GSH (Reduced Glutathione) were estimated and histopathological changes were observed. Group F was excluded after 55% mortality occurred in 15 days. TBARS levels were significantly lower in groups B, C and D than that of control group (A). Catalase was increased significantly in groups C, D and E, whereas SOD increased significantly in groups B, C and D but decreased in group E. Significant increase in GSH in group E and significant reduction in GPx activity in group B were observed. Histopathological studies showed marked focal myocytolysis in group E. These results showed that chronic garlic intake dose dependently augmented endogenous antioxidants, which might have important direct cytoprotective effects on the heart, especially in the event of oxidant stress induced injury.

Chronic garlic administration protects rat heart against oxidative stress induced by ischemic reperfusion injury

BackgroundOxidative stress plays a major role in the biochemical and pathological changes associated with myocardial ischemic-reperfusion injury (IRI). The need to identify agents with a potential for preventing such damage has assumed great importance. Chronic oral administration of raw garlic has been previously reported to augment myocardial endogenous antioxidants. In the present study, the effect of chronic oral administration of raw garlic homogenate on oxidative stress induced by ischemic-reperfusion injury in isolated rat heart was investigated.ResultsRaw garlic homogenate (125, 250 and 500 mg/kg once daily for 30 days) was administered orally in Wistar albino rats. Thereafter, hearts were isolated and subjected to IRI (9 min. of global ischemia, followed by 12 min of reperfusion; perfusion with K-H buffer solution; 37°C, 60 mm Hg.). Significant myocyte injury and rise in myocardial TBARS along with reduction in myocardial SOD, catalase, GSH and GPx were observed following IRI. Depletion of myocardial endogenous antioxidants and rise in TBARS were significantly less in the garlic-treated rat hearts. Oxidative stress induced cellular damage as indicated by ultrastructural changes, like disruption of myofilament, Z-band architecture along with mitochondrial changes were significantly less.ConclusionsThe study strongly suggests that chronic garlic administration prevents oxidative stress and associated ultrastructural changes, induced by myocardial ischemic-reperfusion injury.

Attenuation of insulin resistance, metabolic syndrome and hepatic oxidative stress by resveratrol in fructose-fed rats

Metabolic syndrome and oxidative stress are common complications of type 2 diabetes mellitus. The present study was designed to determine whether resveratrol, a widely used nutritional supplement, can improve insulin sensitivity, metabolic complication as well as hepatic oxidative stress in fructose-fed rats. Male Sprague Dawley rats (180-200 g) were divided into four groups with 8 animals each. Fructose-fed insulin resistant group (Dia) animals were fed 65% fructose (Research diet, USA) for a period of 8 weeks, whereas control group (Con) animals were fed 65% cornstarch (Research Diet, USA). Resveratrol, 10 mg/kg/day (Dia+Resv) or metformin 300 mg/kg/day (Dia+Met) were administered orally to the 65% fructose-fed rats for 8 weeks. At the end of the feeding schedule, Dia group had insulin resistance along with increased blood glucose, triglyceride, uric acid and nitric oxide (NO) levels. Significant (p<0.05) increase in hepatic TBARS and conjugated dienes, and significant (p<0.05) decrease in hepatic SOD and vitamin C was observed in Dia group compared to Con group. Administration of metformin or resveratrol significantly (p<0.05) normalized all the altered metabolic parameters. However, a marked insulin sensitizing action was only observed in the Dia+Resv group. Similarly, while metformin administration failed to normalize the increased TBARS levels and decreased SOD activity, resveratrol showed a more promising effect of all oxidative stress parameters measured in the present study. Attenuation of hepatic oxidative stress in fructose-fed rat liver after resveratrol administration was associated with significant (p<0.05) increase in nuclear level of NRF2 compared with other groups. The present study demonstrates that resveratrol is more effective than metformin in improving insulin sensitivity, and attenuating metabolic syndrome and hepatic oxidative stress in fructose-fed rats.

Studies on antidiarrhoeal activity of Punica granatum seed extract in rats

Methanol extract of Punica granatum seed was evaluated for antidiarrhoeal activity against different experimental models of diarrhoea in rats. P. granatum seed extract treated animals showed significant inhibitory activity against castrol-oil induced diarrhoea and PGE2 induced enteropooling in rats. The extract also showed a significant reduction in gastro-intestinal motility in charcoal meal test in rats. The results obtained established the efficacy of P. granatum seed extract as an antidiarrhoeal agent.

SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states

AIMS Cardiac myocytes depend on a delicate balance of glucose and free fatty acids as energy sources, a balance that is disrupted in pathological states such as diabetic cardiomyopathy and myocardial ischaemia. There are two families of cellular glucose transporters: the facilitated-diffusion glucose transporters (GLUT); and the sodium-dependent glucose transporters (SGLT). It has long been thought that only the GLUT isoforms, GLUT1 and GLUT4, are responsible for cardiac myocyte glucose uptake. However, we discovered that one SGLT isoform, SGLT1, is also an important glucose transporter in heart. In this study, we aimed to determine the human and murine cardiac expression pattern of SGLT1 in health and disease and to determine its regulation. METHODS AND RESULTS SGLT1 was largely localized to the cardiac myocyte sarcolemma. Changes in SGLT1 expression were observed in disease states in both humans and mouse models. SGLT1 expression was upregulated two- to three-fold in type 2 diabetes mellitus and myocardial ischaemia (P < 0.05). In humans with severe heart failure, functional improvement following implantation of left ventricular assist devices led to a two-fold increase in SGLT1 mRNA (P < 0.05). Acute administration of leptin to wildtype mice increased cardiac SGLT1 expression approximately seven-fold (P < 0.05). Insulin- and leptin-stimulated cardiac glucose uptake was significantly (P < 0.05) inhibited by phlorizin, a specific SGLT1 inhibitor. CONCLUSION Our data suggest that cardiac SGLT1 expression and/or function are regulated by insulin and leptin, and are perturbed in disease. This is the first study to examine the regulation of cardiac SGLT1 expression by insulin and leptin and to determine changes in SGLT1 expression in cardiac disease.

Garlic-induced alteration in rat liver and kidney morphology and associated changes in endogenous antioxidant status

The effects of chronic garlic intake on various endogenous antioxidant enzymes and lipid peroxidation on two major organs, the liver (L) and kidneys (K), were investigated. Wistar albino rats were fed with fresh garlic homogenate daily by gavage in three different doses (250, 500 and 1000 mg/kg/day) for 30 days. After this period, rats were sacrificed and liver and kidneys were harvested for biochemical estimation. In comparison to saline-treated rats, the 250 mg/kg/day dose significantly (P<0.02) reduced thiobarbituric acid reactive substances (TBARS) (L: 187.48+/-9.23 vs 150.66+/-11.45; K: 177.38 15.88 vs 120.66+/-9.39 nmol/g wet. weight) and glutathione peroxidase (GPx) (L: 0.2438+/-0.05 vs 0.0046+/-0.0005; K: 0.1459+/-0.034 vs 0.0055+/-0.0003 U/mg protein). There was no change in catalase and reduced glutathione (GSH) but superoxide dismutase (SOD) increased significantly (P<0.01) (L: 5.49+/-0.76 vs 18.38+/-2.26; K: 11.47+/-1.48 vs 21.22+/-3.19 U/mg protein). Both 500 and 1000 mg/kg/day doses significantly (P<0.05) reduced endogenous antioxidants (catalase and SOD) without altering TBARS. A 1000 mg/kg/day dose of garlic caused marked histopathological and ultrastructural changes in both liver and kidneys. The results suggest that garlic in low doses has the potential to enhance the endogenous antioxidant status, although at higher doses a reversal of these effects is observed. The present study also highlights the potential ability of a high dose of garlic to induce morphological changes in the liver and kidneys, indicating the need to identify a safe dose range for garlic.

Garlic improves insulin sensitivity and associated metabolic syndromes in fructose fed rats

BackgroundType 2 diabetes mellitus, characterized by peripheral insulin resistance, is a major lifestyle disorder of the 21st Century. Raw garlic homogenate has been reported to reduce plasma glucose levels in animal models of type 1 diabetes mellitus. However, no specific studies have been conducted to evaluate the effect of raw garlic on insulin resistance or type 2 diabetes mellitus. This study was designed to investigate the effect of raw garlic on fructose induced insulin resistance, associated metabolic syndrome and oxidative stress in diabetic rats.MethodsMale Sprague Dawley rats weighing 200-250 gm body weight were divided into 3 groups (n = 7 per group) and fed diet containing 65% cornstarch (Control group) and 65% fructose (Diabetic group) for 8 weeks. The third group (Dia+Garl group) was fed both 65% fructose and raw garlic homogenate (250 mg/kg/day) for 8 weeks. Whole garlic cloves were homogenized with water to make a fresh paste each day.ResultsAt the end of 8 weeks, serum glucose, insulin, triglyceride and uric acid levels, as well as insulin resistance, as measured by glucose tolerance test, were significantly (p < 0.01) increased in fructose fed rats (Diabetic group) when compared to the cornstarch fed (Control) rats. Administration of raw garlic to fructose fed rats (Dia+Garl group) significantly (p < 0.05) reduced serum glucose, insulin, triglyceride and uric acid levels, as well as insulin resistance when compared with fructose fed rats. Garlic also normalised the increased serum levels of nitric oxide (NO) and decreased levels of hydrogen sulphide (H2S) after fructose feeding. Although body weight gain and serum glycated haemoglobin levels of fructose fed rats (Diabetic group) were not significantly different from control rats, significant (p < 0.05) reduction of these parameters was observed in fructose fed rats after garlic administration (Dia+Garl group). Significant (p < 0.05) increase in TBARS and decrease in GSH was observed in diabetic liver. Catalase was not significantly affected in any of the groups. Administration of raw garlic homogenate normalised both hepatic TBARS and GSH levels.ConclusionsOur study demonstrates that raw garlic homogenate is effective in improving insulin sensitivity while attenuating metabolic syndrome and oxidative stress in fructose-fed rats.